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Treatment Outcome and Analysis of the Prognostic Factors of High Grade Glioma Treated by Postoperative Radiotherapy

고악성도 신경아교종의 수술 후 방사선 치료 성적과 예후인자 분석

  • Lee, Sun-Min (Department of Radiation Oncology, Korea University College of Medicine) ;
  • Park, Young-Je (Department of Radiation Oncology, Korea University College of Medicine) ;
  • Yoon, Won-Sup (Department of Radiation Oncology, Korea University College of Medicine) ;
  • Lee, Suk (Department of Radiation Oncology, Korea University College of Medicine) ;
  • Yang, Dae-Sik (Department of Radiation Oncology, Korea University College of Medicine) ;
  • Jeong, Yong-Gu (Department of Neurosurgery, Korea University College of Medicine) ;
  • Kim, Chul-Yong (Department of Radiation Oncology, Korea University College of Medicine)
  • 이선민 (고려대학교 의과대학 방사선종양학교실) ;
  • 박영제 (고려대학교 의과대학 방사선종양학교실) ;
  • 윤원섭 (고려대학교 의과대학 방사선종양학교실) ;
  • 이석 (고려대학교 의과대학 방사선종양학교실) ;
  • 양대식 (고려대학교 의과대학 방사선종양학교실) ;
  • 정용구 (고려대학교 의과대학 신경외과학교실) ;
  • 김철용 (고려대학교 의과대학 방사선종양학교실)
  • Received : 2010.05.24
  • Accepted : 2010.08.02
  • Published : 2010.09.30

Abstract

Purpose: To analyze the postoperative radiotherapy results and prognostic factors in patients with WHO grade 3 and 4 gliomas. Materials and Methods: A total of 99 patients with malignant gliomas who underwent postoperative radiotherapy between 1988 and 2007 were enrolled in this study. Total resections, subtotal resections ($\geq$50%), partial resections (<50%), and biopsies were performed in 16, 38, 22, and 23 patients, respectively. In total there were 32, 63 and 4 WHO grade 3, 4, and unspecified high grade gliomas, respectively. The biologically equivalent dose was in the range of 18.6 to $83.3\;Gy_{10}$ (median dose, $72.2\;Gy_{10}$). We retrospectively analyzed survival rate, patterns of failure, prognostic factors, and adverse effects. Results: The median follow-up time was 11 months and there were 54 patients (54.5%) with local failure. The one and 2-year survival rates were 56.6% and 29.3%, respectively, and the median survival duration was 13 months. The one and 2-year progression-free survival rates (PFS) were 31.3% and 18.2%, respectively, and the median PFS was 7 months. The prognostic factors for overall survival were age (p=0.0001), surgical extents (subtotal resection, p=0.023; partial resection, p=0.009; biopsy only, p=0.002), and enhancement of tumor in postoperative imaging study (p=0.049). The factors affecting PFS were age (p=0.036), tumor enhancement of the postoperative imaging study (p=0.006). There were 3 patients with grade 3 and 4 side effects during and after radiotherapy. Conclusions: In addition to age and surgical extents, tumor enhancement of the postoperative imaging study was included in the prognostic factors. The most common relapse patterns were local failures and hence, additional studies are needed to improve local control rates.

목 적: WHO 등급 3/4의 신경아교종 환자에서 수술 후 방사선 치료의 결과와 예후인자를 분석하였다. 대상 및 방법: 1988년부터 2007년까지 수술 후 고악성도 신경아교종으로 확진된 환자들 중 방사선 치료를 시행한 99명을 대상으로 하였다. 나이는 18~77세(중앙값, 51세), 남, 여가 각각 55, 44명이었다. 수술은 완전절제, 아전절제(50% 이상 절제), 부분절제(50% 미만 절제), 조직검사만 시행한 예가 각각 16, 38, 22, 23명이었고, WHO 등급 3, 4, 기타(unspecified high grade glioma)가 각각 32, 63, 4명이었다. 방사선 치료는 1.8 또는 2 Gy 통상 분할치료 혹은 1.2 또는 1.5 Gy 하루 2회 치료 방법으로 하였고 중앙 생물학적 등가선량은 $72.2\;Gy_{10}$ ($18.6{\sim}83.3\;Gy_{10}$)였다. 동시항암화학방사선치료나 연속화학방사선요법을 적용한 환자가 49명이었다. 환자들의 생존율 및 실패양상, 예후인자, 부작용에 대해 후향적으로 분석하였다. 결 과: 대상 환자의 중앙 추적 관찰기간은 11개월이었다. 국소치료 실패한 환자가 54명(54.5%)이었고, 이중 12명(22.2%)은 방사선치료부위 밖의 병변 진행을 동반하였다. 전체 생존율은 1년 56.6%, 2년 29.3%였고, 중앙생존기간은 13개월이었다. 무진행생존율은 1년, 2년이 각각 31.3%, 18.2%였으며, 중앙생존기간은 7개월이었다. 전체생존율에 영향을 미치는 인자로는 나이(p=0.0001), 수술 절제 정도(완전절제를 기준으로, 아전절제 p=0.023, 부분절제 p=0.009, 조직생검 p=0.002), 수술 후 영상검사에서 조영증가 여부(p=0.049)였다. 무진행생존율에 영향을 미치는 인자는 나이(p=0.036)와 수술 후 영상검사에서 조영증가 여부(p=0.006)였다. 방사선치료중과 후에 3등급 이상의 부작용이 각각 3명과 1명에서 발생하였다. 결 론: 나이, 수술절제 정도, 수술 후 영상검사에서 조영증가 여부가 생존율에 유의한 요인으로 분석되었다. 국소치료실패가 대부분을 차지하여, 국소 제어율 향상을 위한 추가적인 연구가 필요할 것이다.

Keywords

References

  1. Central Brain Tumor Registry of the United States. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2004-2005. Hinsdale, IL; Central Brain Tumor Registry of the United States, 2009
  2. Stupp R, Dietrich PY, Ostermann Kraljevic S, et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 2002;20:1375-1382 https://doi.org/10.1200/JCO.20.5.1375
  3. Pirtoli L, Rubino G, Marsili S, et al. Three-dimensional conformal radiotherapy, temozolomide chemotherapy, and high-dose fractionated stereotactic boost in a protocol-driven, postoperative treatment schedule for high-grade gliomas. Tumori 2009;95:329-337
  4. Jeon HJ, Kong DS, Park KB, et al. Clinical outcome of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastaomas: single-center experience. Clin Neurol Neurosurg 2009;111:679-682 https://doi.org/10.1016/j.clineuro.2009.06.013
  5. Curran WJ Jr, Scott CB, Horton J, et al. Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst 1993;85:704-710 https://doi.org/10.1093/jnci/85.9.704
  6. Lote K, Egeland T, Hager B, Skullerud K, Hirschberg H. Prognostic significance of CT contrast enhancement within histological subgroups of intracranial glioma. J Neurooncol 1998;40:161-170 https://doi.org/10.1023/A:1006106708606
  7. McGirt MJ, Chaichana KL, Gathinji M, et al. Independent association of extent of resection with survival in patients with malignant brain astrocytoma. J Neurosurg 2009;110:156- 62 https://doi.org/10.3171/2008.4.17536
  8. Mirimanoff RO, Gorlia T, Mason W, et al. Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol 2006;24:2563-2569 https://doi.org/10.1200/JCO.2005.04.5963
  9. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009;10:459-466 https://doi.org/10.1016/S1470-2045(09)70025-7
  10. Hochberg FH, Pruitt A. Assumptions in the radiotherapy of glioblastoma. Neurology 1980;30:907-911 https://doi.org/10.1212/WNL.30.9.907
  11. Wallner KE, Galicich JH, Krol G, Arbit E, Malkin MG. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys 1989; 16:1405-1409 https://doi.org/10.1016/0360-3016(89)90941-3
  12. Cho H, Choi Y. Optimal radiation therapy field for malignant astrocytoma and glioblastoma multiforme. J Korean Soc Ther Radiol Oncol 2002;20:199-205
  13. Souhami L, Seiferheld W, Brachman D, et al. Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys 2004;60:853-860 https://doi.org/10.1016/j.ijrobp.2004.04.011
  14. Cardinale R, Won M, Choucair A, et al. A phase II trial of accelerated radiotherapy using weekly stereotactic conformal boost for supratentorial glioblastoma multiforme: RTOG 0023. Int J Radiat Oncol Biol Phys 2006;65:1422-1428 https://doi.org/10.1016/j.ijrobp.2006.02.042
  15. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31:1341-1346 https://doi.org/10.1016/0360-3016(95)00060-C
  16. Minniti G, De Sanctis V, Muni R, et al. Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma. J Neurooncol 2009;91:95-100 https://doi.org/10.1007/s11060-008-9689-z
  17. Dhermain F, Saliou G, Parker F, et al. Microvascular leakage and contrast enhancement as prognostic factors for recurrence in unfavorable low-grade gliomas. J Neurooncol 2010;97:81-88 https://doi.org/10.1007/s11060-009-9992-3
  18. McLendon RE, Halperin EC. Is the long-term survival of patients with intracranial glioblastoma multiforme overstated? Cancer 2003;98:1745-1748 https://doi.org/10.1002/cncr.11666
  19. Senger D, Cairncross JG, Forsyth PA. Long-term survivors of glioblastoma: statistical aberration or important unrecognized molecular subtype? Cancer J 2003;9:214-221 https://doi.org/10.1097/00130404-200305000-00009
  20. Chan JL, Lee SW, Fraass BA, et al. Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J Clin Oncol 2002;20:1635-1642 https://doi.org/10.1200/JCO.20.6.1635
  21. Benito R, Gil-Benso R, Quilis V, et al. Primary glioblastomas with and without EGFR amplification: relationship to genetic alterations and clinicopathological features. Neuropathology 2010;30:392-400